MT3-MMP down-regulation promotes tumorigenesis and correlates to poor prognosis in esophageal squamous cell carcinoma

作者：Xue, Zengfu^*; Wu, Xiumin; Chen, Xiong; Luo, Qi^*

来源：Cancer Medicine, 2016, 5(9): 2459-2468.

DOI：10.1002/cam4.790

• Cell cycle
• esophageal squamous cell carcinoma
• immunohistochemistry
• MT3-MMP
• prognosis

The membrane-type matrix metalloproteinases (MT-MMPs) play an important role in degrading the extracellular matrix (ECM) and facilitating protease-dependent tumor progression and invasion. Here, we report that unlike MT1-MMP, MT3-MMP was down-regulated in esophageal squamous cell carcinoma (ESCC) as detected by real-time PCR (qPCR), Western blot analysis, and immunohistochemistry (IHC). Down-regulation of MT3-MMP was observed at protein level in 66.3% of ESCC specimens (by IHC, n=86) for routine pathologic diagnosis, as well as at mRNA level in 63.3% of surgically resected ESCC tumors paired with surrounding nontumor tissues (by qPCR, n=30). Notably, MT3-MMP down-regulation significantly correlated with lymph node metastasis and poor overall survival of patients with ESCC (median 5-year survival=50.69 vs. 30.77months for patients with MT3-MMP-negative and -positive ESCC, respectively). Mechanistically, MT3-MMP negatively regulated proliferation, colony formation, and migration of ESCC cells, in association with cell cycle arrest at G1, due to up-regulation of p21(Cip1) and p27(Kip1). Together, as a tumor suppressor in ESCC, MT3-MMP down-regulation represents an unfavorable factor for prognosis of patients with ESCC.

• 出版日期2016-9
• 单位厦门大学